for people ages 18 years and up (full criteria)
at Orange, California and other locations
study started
completion around



This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Substudy 04A will enroll participants with locally advanced or mUC whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors. The protocol infrastructure will enable the rolling assignment of investigational treatments.

Official Title

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A


Urothelial Carcinoma, Carcinoma, Transitional Cell Carcinoma, Zilovertamab vedotin


You can join if…

Open to people ages 18 years and up

The main inclusion and exclusion criteria include but are not limited to the following:

  • Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
  • PD-1/L1 refractory locally advanced or mUC as evidenced by:

EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.

  • Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation.

You CAN'T join if...

  • Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.
  • Active infection requiring systemic therapy.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
  • Known history of human immunodeficiency virus (HIV).
  • Known history of hepatitis B or known hepatitis C virus infection.


  • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
    Orange California 92868 United States
  • Anschutz Cancer Pavilion ( Site 1017)
    Aurora Colorado 80045 United States


in progress, not accepting new patients
Start Date
Completion Date
Merck Sharp & Dohme LLC
Merck Oncology Clinical Trials Information
Phase 1/2 research study
Study Type
Expecting 40 study participants
Last Updated